PB1985: FACTORS ASSOCIATED WITH TOLERANCE TO PHARMACOLOGICAL THERAPY USING TYROSINE KINASE INHIBITORS IN CHRONIC MYELOID LEUKEMIA PATIENTS ATTENDED AT FOSCAL IN THE PERIOD 2013-2020.
Authors: Claudia Lucía Sossa, Néstor Gamboa, Luis Antonio Salazar, Ángela María Peña, Gabriela Vesga-Jerez, Ana María Prada-Sepúlveda, María Luna-González, Manuel Rosales, Miguel Ochoa, Virginia Abello
Journal: HemaSphere (2023)

Topic: 8. Chronic myeloid leukemia - Clinical Background: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by BCR/ABL fusion gene presence and its activity through tyrosine kinase activation. Therefore, the introduction of Tyrosine Kinase Inhibitors (TKIs) reduced mortality to 1-2%. TKIs are classified by generations: first (Imatinib), second (Nilotinib, Dasatinib and Bosutinib) and third (Ponatinib). The molecular response, resistance, adverse effects and tolerance vary according to TKIs generation. Aims: The aim of this study was to determine the association between clinical characteristics and tolerance to pharmacological therapy with TKIs. Methods: Secondary analysis of an anonymized database of CML patients attended at FOSCAL and included in RENEHOC (online platform). Univariate analysis was performed to characterize the population, and bivariate for Relative Risk (RR) effect measures. STATA V14 was used as a statistical package. The institutional ethics committee gave approval (06223/2022). Results: A total of 122 patients attended at FOSCAL in the period 2013-2020. The mean age was 56 years (SD 16) and 55% were women. Regarding comorbidities, 23.7% of patients had arterial hypertension (AHT) and 9% had hypercholesterolemia. During the first line of treatment, patients took: Imatinib (67.5%), Dasatinib (20.5%) and Nilotinib (6.5%). Data from 102 patients showed that 48% had toxicity with a mean age of 60 years (SD 14.2), corresponding to 56.3% of all men and 13.7% of all hypertensive patients. Toxicity risk was found for men RR: 1.38 (95%CI:0.92-2.07; p=0.11), age RR: 1 (95%CI:0.99-1-02; p=0.12) and arterial hypertension RR: 1.11 (95%CI:0.72-1.72; p=0.63). In risk indexes, having a higher score in Sokal index represented lower toxicity (52.9%) RR: 0.98 (95%CI:0.51-1.9; p=0.96 while having a higher score in Hasford index represented more toxicity (71.4%) with RR: 1.81 (95%CI:0.96-3.41; p=0.06). Evaluating TKIs safety profile, 71% of those treated with Imatinib did not present toxicity, and of those who presented, 59% were hematologic and 12% were hepatic. In those who received Dasatinib, 55% developed toxicity, most with pulmonary presentation (30%), followed by hematologic toxicity in 26%. Using Nilotinib, 52% presented toxicity, 34% of which was hematologic and 20% cutaneous (Image 1). Summary/Conclusion: Adverse effects of TKIs have a significant role for therapy selection; Drug tolerance varies according to patient features and comorbidities. Imatinib use was associated with higher tolerance, as well as high risk at Hasbord index, although the difference was not statistically significant. Hypertension has commonly been associated with higher risk of toxicity, nevertheless our data showed no statistical difference.Keywords: Tyrosine kinase inhibitor, Chronic myeloid leukemia, Toxicity